Docetaxel, which belongs to taxoids, is an anti-cancer chemotherapeutic agent having a broad spectrum of anti-tumor and anti-leukemia activities. It is a semi-synthesized anti-cancer drug obtained by chemical modification of 10-deactylbaccatin III which is extracted from leaves and barks of Europe or India Yew tree, and has been approved as a marketable therapeutic agent against breast cancer and ovarian cancer, etc. in many countries including Europe.
Although a method of recrystallization using acetone and hexane, and a method of recrystallization using acetonitrile and purified water are currently known to prepare anhydrous crystalline docetaxel by recrystallizing semi-synthesized docetaxel, a method of recrystallization using dichloromethane and hexane, these methods lead to anhydrous crystalline docetaxel with markedly low purity. Particularly, it is very important to increase purity of docetaxel for medical use.
Particularly, in the preparation of highly pure anhydrous crystalline docetaxel, it is difficult to remove impurities or residual solvents. During preparation of anhydrous crystalline docetaxel, stability of docetaxel is destroyed and impurities such as 7-epimer, i.e., 4-acetoxy-2α-benzoyloxy-5-β, 20-epoxy-1,7β,10β-trihydroxy-9-oxo-tac-11-ene-1 3-α-yl(2R,3S)-3-t-butoxycarbonylamino-2′-hydroxy-3-phenylpropionate are generated. Thus, it is very difficult to prepare highly pure anhydrous crystalline docetaxel.
Accordingly, there is a demand for development of a method for preparing highly pure anhydrous crystalline docetaxel having low impurity contents.